Response to Selpercatinib in a Patient With Recurrent Glioblastoma and RET Amplification

Authors: Cameron Czech PharmD1,2,3, Ashley Chen PharmD1,2,4, Katherine P. Morgan PharmD, BCOP, CPP1,2, Carlos Zamora MD, PhD5, Sherif El-Refai PharmD, PhD, MBA6, Norleena Poynter MD7, and Simon Khagi MD8,9,10,11
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  • 1 Department of Pharmacy, University of North Carolina Medical Center, Chapel Hill, North Carolina;
  • | 2 Department of Practice Advancement and Clinical Education, University of North Carolina Eshelman School of Pharmacy, Chapel Hill, North Carolina;
  • | 3 Now with Exelixis Inc., Alameda, California;
  • | 4 Now with Department of Pharmacy, University of Washington Medical Center, Seattle, Washington;
  • | 5 Division of Neuroradiology, Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina;
  • | 6 Tempus Laboratories Inc., Chicago, Illinois;
  • | 7 Department of Radiation Oncology, Duke University Health System, Scotland Cancer Treatment Center, Durham, North Carolina;
  • | 8 Division of Medical Oncology, Department of Medicine, and
  • | 9 Department of Neurosurgery, University of North Carolina School of Medicine, Chapel Hill, North Carolina;
  • | 10 Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina; and
  • | 11 Now with Department of Medicine, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.

Glioblastoma (GBM) is a malignant central nervous system neoplasm that remains largely incurable. Limited treatment options currently exist after disease progression on standard-of-care first-line therapy. However, repurposing the use of approved therapies in patients with potentially targetable genomic alterations continues to be an emerging area of interest. This report presents the first description of a patient with isocitrate dehydrogenase wild-type GBM with an underlying RET amplification who demonstrated a near-complete response while receiving therapy with the RET inhibitor selpercatinib. The case highlights the excellent blood-brain barrier penetration of selpercatinib, as well as its potential role in the management of RET-amplified GBM. Larger biomarker-enriched studies are needed to confirm the results of this case report. Given the rare incidence of RET alterations in GBM, findings from this report can help guide and support optimal treatment strategies for patients with RET-altered GBM.

Submitted August 4, 2021; final revision received May 8, 2022; accepted for publication May 9, 2022.

Disclosures: Dr. Czech has disclosed being employed by Exelixis, Inc. Dr. El-Refai has disclosed owning stock and having other ownership interests in Tempus Labs, Inc. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Correspondence: Simon Khagi, MD, Dartmouth Cancer Center Manchester, Notre Dame Pavilion, 87 McGregor Street, Manchester, NH 03102. Email: simon.khagi@hitchcock.org
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